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Expert Rev Vaccines. 2014 Oct;13(10):1215-27. doi: 10.1586/14760584.2014.944900. Epub 2014 Aug 4.

Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines.

Author information

1
Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i, Videnska 1083, 142 20, Prague 4, Czech Republic.

Abstract

The adenylate cyclase toxin-hemolysin (ACT, AC-Hly or CyaA) is a key virulence factor of Bordetella pertussis. It targets bactericidal activities of phagocytes, such as oxidative burst and complement- or antibody-mediated opsonophagocytic killing of bacteria. Through cAMP signaling, CyaA also skews TLR-triggered maturation of dendritic cells, inhibiting proinflammatory IL-12 and TNF-α secretion and enhancing IL-10 production and Treg expansion, likely hampering induction of adaptive immune responses to Bordetella infections. Non-enzymatic CyaA toxoid is a potent protective antigen and adjuvant that boosts immunogenicity of co-administered B. pertussis antigens and improves potency of acellular pertussis (aP) vaccines in mice. This makes CyaA a prime antigen candidate for inclusion into a next generation of aP vaccines. Moreover, recombinant CyaA toxoids were recently shown to be safe in humans in frame of Phase I clinical evaluation of a CyaA-based immunotherapeutic vaccine that induces Th1-polarized CD8(+) cytotoxic T-lymphocyte responses targeting cervical tumors.

KEYWORDS:

Bordetella pertussis; T-cell epitope; T-cell vaccine; adenylate cyclase toxin; antigen delivery; cancer immunotherapy; complement receptor 3; dendritic cell; pertussis; pertussis vaccine; whooping cough

PMID:
25090574
DOI:
10.1586/14760584.2014.944900
[Indexed for MEDLINE]

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